miR-let-7d regulates lung cancer cell proliferation and invasion abilities through nuclear receptor PPARγ / 中国病理生理杂志

AIM: To investigate the phenomenon that miR-let-7d regulates the proliferation and invasion abilities of the lung cancer cells through nuclear receptor peroxisome proliferator-activated receptors γ (PPARγ).METHODS: The relation between PPARγ and microRNA was analyzed by bioinformatics.The plasmid reporter assay was used to verify that PPARγ was the target of miR-let-7d.The lung cancer cell line with low expression of PPARγ was selected from different lung cancer cell lines by Western blot.The regulatory role of miR-let-7d in the lung cancer cells was determined by dual luciferase labeling and Western blot.The effect of miR-let-7d on the proliferation ability of lung cancer cells was detected by colony formation assay, the effect of miR-let-7d on the invasive ability of lung cancer cells was detected by Transwell invasion assay.RESULTS: The results of bioinformatic analysis showed that miR-let-7d regulated the expression of PPARγ, and the 3'UTR of PPARγ contained 2 functional miR-let-7d binding sites, indicating that PPARγ is a direct target of miR-let-7d.miR-let-7d was able to directly regulate the expression of PPARγ at mRNA and protein levels.Transfection of miR-let-7d inhibitor promoted the proliferation and invasion abilities of lung cancer cells by increasing the expression of PPARγ.CONCLUSION: miR-let-7d increases the expression of tumor suppressor PPARγ to inhibit the proliferation and invasive abilities of lung cancer cells.

Rosiglitazone inhibits osteoclastogenesis in rheumatoid arthritis by down-regulating RANKL expression and suppressing ERK phosphorylation / 中国病理生理杂志

AIM: To investigate the effects of rosiglitazone on fibroblast-like synoviocyte ( FLS )-induced osteoclastogenesis in rheumatoid arthritis ( RA) and the related mechanism.METHODS: RA-FLS were cocultured with peripheral blood monocytes from healthy volunteers in the presence of macrophage colony-stimulating factor ( M-CSF) and rosiglitazone.Osteoclasts were assayed by tartrate-resistant acid phosphatase ( TRAP) staining.Resorption lacunae area was identified by toluidine blue staining and quantified by image analysis software.The mRNA expression of RANKL and OPG was evaluated by real-time PCR, and the protein levels of RANKL, OPG, p-ERK, p-p38 and p-JNK were measured by Western blot.RESULTS:Compared with control group ( without rosiglitazone treatment) , rosiglitazone at concentration of 15 μmol/L significantly decreased the number of osteoclasts (P0.05 ) . CONCLUSION:Rosiglitazone inhibits RA-FLS-induced osteoclast formation and its resorption activity by down-regulating RANKL expression and ERK phosphorylation, suggesting that rosiglitazone may inhibit RA osteoclastogenesis and bone re-sorption.